Variant X-40623602-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001195522.3(MPC1L):c.37G>A(p.Asp13Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,094,329 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000010 ( 0 hom. 3 hem. )

Consequence

MPC1L
NM_001195522.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.662

Variant links:

Genes affected

MPC1L (HGNC:44205): (mitochondrial pyruvate carrier 1 like) Predicted to enable pyruvate transmembrane transporter activity. Predicted to be involved in mitochondrial pyruvate transmembrane transport. Predicted to be integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

MPC1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07221407).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPC1L	NM_001195522.3 linkuse as main transcript	c.37G>A	p.Asp13Asn	missense_variant	1/1	ENST00000423387.4	NP_001182451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPC1L	ENST00000423387.4 linkuse as main transcript	c.37G>A	p.Asp13Asn	missense_variant	1/1		NM_001195522.3	ENSP00000489748	P1

Frequencies

GnomAD3 genomes

AF:

0.0000713

AC:

AN:

112270

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34412

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

982059

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

310157

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000713

AC:

AN:

112270

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34412

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.37G>A (p.D13N) alteration is located in exon 1 (coding exon 1) of the MPC1L gene. This alteration results from a G to A substitution at nucleotide position 37, causing the aspartic acid (D) at amino acid position 13 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.2

DANN

Benign

0.79

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.35

MetaRNN

Benign

0.072

MutationAssessor

Benign

0.52

PrimateAI

Benign

0.44

GERP RS

2.5

Varity_R

0.040

gMVP

0.040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over